Review
Microbiology
Marta Mendonca Cova, Mauld H. Lamarque, Maryse Lebrun
Summary: This review covers the molecular advances of microneme and rhoptry exocytosis in Apicomplexa, focusing on how the proteins released from these compartments work together to drive successful invasion.
ANNUAL REVIEW OF MICROBIOLOGY
(2022)
Article
Biology
Daniel N. A. Tagoe, Allison A. Drozda, Julia A. Falco, Tyler J. Bechtel, Eranthie Weerapana, Marc-Jan Gubbels
Summary: The invasion process of apicomplexan parasites like Toxoplasma gondii into host cells is facilitated by the sequential exocytosis of microneme, rhoptry, and dense granule organelles. The DOC2 protein family plays a key role in this exocytosis process and Ca2+ helps engage C2 domains with lipids, membranes, and proteins for vesicular trafficking and membrane fusion. Ferlins are important for microneme and rhoptry exocytosis in T. gondii, with ferlins facilitating membrane fusion without SNAREs, especially in apicomplexan parasites.
Article
Biochemistry & Molecular Biology
Daniela Sparvoli, Jason Delabre, Diana Marcela Penarete-Vargas, Shrawan Kumar Mageswaran, Lev M. Tsypin, Justine Heckendorn, Liam Theveny, Marjorie Maynadier, Marta Mendonca Cova, Laurence Berry-Sterkers, Amandine Guerin, Jean-Francois Dubremetz, Serge Urbach, Boris Striepen, Aaron P. Turkewitz, Yi-Wei Chang, Maryse Lebrun
Summary: A membrane-bound protein complex called CRMPs has been discovered to play a crucial role in rhoptry secretion and invasion in Toxoplasma. Unlike previously described rhoptry exocytic factors, TgCRMPs are not essential for the assembly of the rhoptry secretion machinery and only transiently associate with the exocytic site prior to invasion. The CRMP complex seems to act as a host-molecular sensor to ensure rhoptry exocytosis occurs when the parasite contacts the host cell.
Article
Biochemistry & Molecular Biology
Dylan Valleau, Saima M. Sidik, Luiz C. Godoy, Yamilex Acevedo-Sanchez, Charisse Flerida A. Pasaje, My-Hang Huynh, Vern B. Carruthers, Jacquin C. Niles, Sebastian Lourido
Summary: The microneme protein CLAMP, along with the invasion-associated SPATR and a previously uncharacterized protein CLAMP-linked invasion protein (CLIP), forms a complex that is essential for rhoptry discharge following host-cell contact. Phylogenetic analysis suggests that the essential complex components are present across apicomplexans.
Article
Biology
Amit Kumar, Oscar Vadas, Nicolas Dos Santos Pacheco, Xu Zhang, Kin Chao, Nicolas Darvill, Helena O. Rasmussen, Yingqi Xu, Gloria Meng-Hsuan Lin, Fisentzos A. Stylianou, Jan Skov Pedersen, Sarah L. Rouse, Marc L. Morgan, Dominique Soldati-Favre, Stephen Matthews
Summary: The intracellular parasites belonging to the phylum of Apicomplexa employ substrate-dependent gliding motility to invade host cells. The glideosome-associated connector (GAC), a conserved protein, plays a crucial role in this process. The crystal structure of Toxoplasma gondii GAC reveals a unique armadillo repeat region that adopts a closed ring conformation. The properties of GAC suggest that it can adopt multiple conformations from closed to open and extended, and a multi-conformational model is proposed for its assembly and regulation within the glideosome.
Article
Microbiology
Nicolas Dos Santos Pacheco, Nicolo Tosetti, Aarti Krishnan, Romuald Haase, Bohumil Maco, Catherine Suarez, Bingjian Ren, Dominique Soldati-Favre
Summary: Depletion of ERK7 in Toxoplasma gondii disrupts the integrity of the apical complex, leading to the loss of the apical polar ring and impairment in microneme secretion. Comparative proteomics analysis reveals the disappearance of known apical complex proteins and the accumulation of microneme proteins.
Article
Multidisciplinary Sciences
Zhu-Hong Li, Thayer P. King, Lawrence Ayong, Beejan Asady, Xinjiang Cai, Taufiq Rahman, Stephen A. Vella, Isabelle Coppens, Sandip Patel, Silvia N. J. Moreno
Summary: This study characterizes a TPC from Toxoplasma gondii that localizes to the apicoplast, playing a critical role in maintaining its integrity and facilitating Ca2+ uptake from the ER through stabilizing inter-organelle contact.
NATURE COMMUNICATIONS
(2021)
Article
Parasitology
Yang Wang, Chengjian Han, Rongsheng Zhou, Jinjin Zhu, Famin Zhang, Jingyang Li, Qingli Luo, Jian Du, Deyong Chu, Yihong Cai, Jilong Shen, Li Yu
Summary: The study revealed significant differences in the protein level of TgMIC1 between the high-virulence strain TgCtwh3 and low-virulence strain TgCtwh6, with the TgMIC1 polyclonal antibody inhibiting the invasion and proliferation of TgCtwh3. These findings suggest that the differential expression of TgMIC1 may partly explain the virulence mechanism in this atypical genotype.
PARASITES & VECTORS
(2021)
Article
Biology
Karla Marie Marquez-Nogueras, Miryam Andrea Hortua Triana, Nathan M. Chasen, Ivana Y. Kuo, Silvia N. J. Moreno
Summary: This study identified a novel ion channel, TgTRPPL-2, in Toxoplasma gondii that plays a role in Ca2+ signaling and may stimulate parasite motility, invasion, and egress through a Ca2+ signaling cascade. TgTRPPL-2 represents a potential target for combating toxoplasmosis.
Review
Immunology
Chanjin Yoon, Yu Seong Ham, Woo Jin Gil, Chul-Su Yang
Summary: This review article provides an overview of the activation and specific role of the NLRP3 inflammasome in Toxoplasma gondii infection. It points out that the role of NLRP3 inflammasome in T. gondii infection is still uncertain and the mechanisms of its activation in different cell types are still unknown.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Microbiology
Adeline Ribeiro E. Silva, Mamadou Amadou Diallo, Alix Sausset, Thomas Robert, Stephane Bach, Francoise I. Bussiere, Fabrice Laurent, Sonia Lacroix-Lamande, Anne Silvestre
Summary: This study described the second ROP kinase expressed at the sporozoite stage in E. tenella, named EtROP2. It was found that EtROP2 activates the p38 MAPK pathway through direct or indirect phosphorylation, leading to the overexpression of the master transcription factor cFos. These findings are important for understanding the development of Eimeria tenella and for controlling its growth.
MICROBIOLOGY SPECTRUM
(2023)
Article
Microbiology
David J. Dubois, Sylia Chehade, Marq Jean-Baptiste, Kannan Venugopal, Bohumil Maco, Albert Tell I. Puig, Dominique Soldati-Favre, Sabrina Marion
Summary: This study identifies TgHOOK and TgFTS as endosomal trafficking regulators involved in the apical exocytosis of micronemes. They form a complex with TgHIP and regulate organelle positioning and secretion, impacting processes such as egress, motility, and host cell invasion.
Article
Multidisciplinary Sciences
Asma S. Khelifa, Cecilia Guillen Sanchez, Kevin M. Lesage, Ludovic Huot, Thomas Mouveaux, Pierre Pericard, Nicolas Barois, Helene Touzet, Guillemette Marot, Emmanuel Roger, Mathieu Gissot
Summary: Khelifa et al. identified a key transcriptional regulator, TgAP2IX-5, in the model Apicomplexan Toxoplasma gondii, which controls the timing of daughter cell emergence and regulates the expression of necessary transcription factors for completion of the budding cycle. Additionally, TgAP2IX-5 acts as a limiting factor by promoting the inhibition of the differentiation pathway, ensuring the continuation of asexual proliferation.
NATURE COMMUNICATIONS
(2021)
Article
Microbiology
Alessia Possenti, Manlio Di Cristina, Chiara Nicastro, Matteo Lunghi, Valeria Messina, Federica Piro, Lorenzo Tramontana, Simona Cherchi, Mario Falchi, Lucia Bertuccini, Furio Spano
Summary: This study identifies and characterizes two thrombospondin-related proteins, RDF1 and RDF2, in Toxoplasma gondii, showing their key roles in controlling rhoptry discharge, and uncovers a compensatory mechanism contributing to phenotypic plasticity in T. gondii.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Immunology
David Arranz-Solis, Cristina G. Carvalheiro, Elizabeth R. Zhang, Michael E. Grigg, Jeroen P. J. Saeij
Summary: The severity of toxoplasmosis is determined by a combination of host and parasite factors, with the strain type being a key determinant. Serological typing offers a promising alternative to biopsy-based DNA methods, but improvements in sensitivity and specificity are still needed. An ELISA-based assay using immunogenic Toxoplasma peptides can discriminate between archetypal and nonarchetypal strains infecting mice and humans, offering diagnostic potential for strain identification.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Saskia Egarter, Jorge M. Santos, Jessica Kehrer, Julia Sattler, Friedrich Frischknecht, Gunnar R. Mair
Summary: Studies have revealed that LIMP protein plays a crucial role in malaria transmission by affecting the invasion of ookinetes and parasite infection. Parasites lacking LIMP exhibit significantly reduced oocyst numbers and infectivity despite normal morphology and in vitro gliding motility.
MOLECULAR AND BIOCHEMICAL PARASITOLOGY
(2021)
Article
Cell Biology
Mirko Singer, Friedrich Frischknecht
Summary: The study investigated the role of CSP in Plasmodium sporozoites formation, egress, and invasion, by inserting green fluorescent protein at specific positions, revealing that different insertion sites can affect the formation of sporozoites.
CELLULAR MICROBIOLOGY
(2021)
Article
Medicine, Research & Experimental
Johanna Ripp, Jessica Kehrer, Xanthoula Smyrnakou, Nathalie Tisch, Joana Tavares, Rogerio Amino, Carmen Ruiz de Almodovar, Friedrich Frischknecht
Summary: The transmission of malaria-causing parasites is dependent on active parasite migration facilitated by environmental conditions. Ookinetes and sporozoites, two stages of the parasite, adapt different migration strategies to overcome physical challenges posed by different environments, including substrate elasticity.
EMBO MOLECULAR MEDICINE
(2021)
Editorial Material
Biochemistry & Molecular Biology
Julien Guizetti, Friedrich Frischknecht
Summary: The discovery of a conserved ring structure in apicomplexan parasites challenges the long-standing paradigm, indicating a crucial element present throughout the entire phylum.
Review
Cell Biology
Sujaan Das, Johannes Felix Stortz, Markus Meissner, Javier Periz
Summary: Actin, a highly abundant and conserved cytoskeletal protein in eukaryotic cells, plays critical roles in various cellular functions. Different isoforms of actin may have regulated expression patterns and unique roles, possibly influenced by selective pressure from actin binding proteins. The regulation and biological functions of actin in apicomplexans, with fewer actin binding proteins, are still unclear.
CELLULAR MICROBIOLOGY
(2021)
Article
Biochemical Research Methods
Elias B. Farr, Julia M. Sattler, Friedrich Frischknecht
Summary: SPOT is a web tool for comparative analysis and ranking of gene expression profiles, allowing users to export the best results as Excel files. The tool has been tested on data from malaria parasites and SARS-CoV-2 infected cell lines.
Article
Parasitology
Sebastian Miles, Javier Magnone, Joaquin Garcia-Luna, Maria Eugenia Ancarola, Marcela Cucher, Sylvia Dematteis, Friedrich Frischknecht, Marek Cyrklaff, Gustavo Mourglia-Ettlin
Summary: This study provides an in-depth characterization of the tegument of Echinococcus ortleppi protoscoleces, revealing a novel structure termed the 'tegumental vesicular body' and vesicle-like structures possibly involved in endocytic/exocytic routes. Parasite antigens were unevenly localized within tegumental structures, with both being detected in vesicles found within the TVB. The presence of host IgG suggests a possible endocytic route in protoscoleces.
INTERNATIONAL JOURNAL FOR PARASITOLOGY
(2021)
Editorial Material
Parasitology
Markus Ganter, Friedrich Frischknecht
Summary: Plasmodium merozoites invade erythrocytes through ligand binding, calcium signaling, and membrane deformation in a stepwise manner. Geoghegan et al. utilized a newly developed light sheet microscope to investigate invasion with unprecedented temporal resolution, revealing the roles of host cell cholesterol and pore formation at the parasite-host cell interface.
TRENDS IN PARASITOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Jessica Kimmel, Jessica Kehrer, Friedrich Frischknecht, Tobias Spielmann
Summary: In the past 10 years, proximity-dependent biotinylation (PDB) techniques have been widely used, particularly for detecting protein interactions under physiological conditions and studying cellular structures with unclear protein composition. New PDB methods offer improved temporal and spatial resolution, with broad application potential for research on apicomplexan parasites.
MOLECULAR MICROBIOLOGY
(2022)
Article
Microbiology
Wei Li, Janessa Grech, Johannes Felix Stortz, Matthew Gow, Javier Periz, Markus Meissner, Elena Jimenez-Ruiz
Summary: Using a conditional Cas9-system, a phenotypic screen identified two genes in Toxoplasma gondii that play different roles in host cell egress. This method helps overcome the difficulty of assigning gene functions in apicomplexan parasites and has potential for identifying more related genes in future studies.
NATURE MICROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Severina Klaus, Patrick Binder, Juyeop Kim, Marta Machado, Charlotta Funaya, Violetta Schaaf, Darius Klaschka, Aiste Kudulyte, Marek Cyrklaff, Vibor Laketa, Thomas Hoefer, Julien Guizetti, Nils B. Becker, Friedrich Frischknecht, Ulrich S. Schwarz, Markus Ganter
Summary: This study shows that individual nuclei replicate their DNA at different times, despite sharing a common cytoplasm. Mathematical modeling suggests the existence of a limiting factor that slows down nuclear multiplication. Experimental data supports the prediction that temporally overlapping DNA replication events are slower than partially or non-overlapping events. These findings suggest the presence of evolutionary pressure that selects for asynchronous DNA replication to balance resources and rapid pathogen proliferation.
Article
Biology
Jessica Jin, Mame Aida Ba, Chi Ho Wai, Sanjib Mohanty, Praveen K. Sahu, Rajyabardhan Pattnaik, Lukas Pirpamer, Manuel Fischer, Sabine Heiland, Michael Lanzer, Friedrich Frischknecht, Ann-Kristin Mueller, Johannes Pfeil, Megharay Majhi, Marek Cyrklaff, Samuel C. Wassmer, Martin Bendszus, Angelika Hoffmann
Summary: This study shows that reversible brain swelling in experimental murine cerebral malaria (CM) can be induced reliably after single vaccination with radiation-attenuated sporozoites, and it is suggested that transcellular blood-brain barrier disruption (BBBD) is responsible for the brain swelling. Although brain swelling can be reversed, it does not prevent persistent focal brain damage in the areas of most severe BBBD.
LIFE SCIENCE ALLIANCE
(2022)
Article
Biochemistry & Molecular Biology
Mirko Singer, Kathrin Simon, Ignasi Forne, Markus Meissner
Summary: Apicomplexa are parasites that live inside cells and are restricted to specific hosts and cell types. However, Toxoplasma gondii can invade any nucleated cell from warm-blooded animals, indicating a broad host range due to recognition of multiple host cell ligands or structures. During invasion, secretory organelles are released and certain micronemal proteins are suggested to be essential. The Cysteine Repeat Modular Proteins (CRMPs) form a complex with other proteins, and disruption of this complex inhibits rhoptry secretion and host cell invasion, suggesting its conservation in all apicomplexans.
Article
Cell Biology
Mirjam Wagner, Yuan Song, Elena Jimenez-Ruiz, Sonja Hartle, Markus Meissner
Summary: Connections between the nucleus and the cytoskeleton are crucial for nucleus positioning and division. This study identifies UNC family proteins in the genome of the apicomplexan parasite T. gondii and demonstrates their roles and localization in the parasite.
JOURNAL OF CELL SCIENCE
(2023)
Review
Biochemistry & Molecular Biology
Elena Jimenez-Ruiz, Wei Li, Markus Meissner
Summary: Apicomplexans are intracellular parasites that invade, replicate, and exit host cells. During replication, they establish an F-actin-containing network within a parasitophorous vacuole, which is essential for material exchange and daughter cell assembly. Exiting the host cell involves multiple signalling cascades, network disassembly, microneme protein secretion, and acto-myosin motor activation. Recent technological developments, including genetic and phenotypic screens using random insertion mutagenesis, temperature-sensitive mutants, and CRISPR/Cas9-mediated targeted editing, have led to the identification of new critical factors in Toxoplasma gondii.
MOLECULAR MICROBIOLOGY
(2023)
